occurs in the glomerulus where blood is filtered to generate a fluid (that makes its way into the renal tubule) free of cells & most proteins

it looks like plasma MINUS the proteins

Reabsorption

most of the filtered water & solutes (eg. Na+, Cl-, glucose, etc.) are reabsorbed from the tubular fluid

the vast majority of processing that occurs in the renal tubule IS reabsorption

what’s left behind in the tubular fluid are substances the body wants to excrete (via urine)

Secretion

the selective process of transporting solutes into the renal fluid (in the renal tubule)

solutes (uric acid) & ions (K+, Fe) are some compounds along w/ other organic anions & cations that can be secreted INTO the tubular fluid

(the bulk of processing is reabsorption not secretion though)

Excretion

excretion is what makes up the urine after all the processing has occurred

what’s excreted consists of the water & solutes that remain in the tubular fluid after passing through the renal tubule

*Excretion = Filtration - Reabsorption + Secretion

What plasma electrolytes do the kidneys control the concentration of?

Na+

K+

Cl-

HCO3-

Ca2+

PO43-

(to name a few)

What is the primary role the kidney plays in controlling plasma pH?

it can reabsorb filtered bicarbonate (HCO3-)

the vast majority of bicarb filtered by the glomerulus is REABSORBED in the proximal tubule

What is a secondary way the kidneys help control plasma pH?

they can selectively secrete acid (H+)

this happens in the intercalating cells of the collecting duct (CD) - these cells have the capacity to secrete acid directly into the urine

What two hormones are synthesized & released by the kidney?

Renin: increases blood pressure

Erythropoietin: regulates RBC production in bone marrow

If a compound is filtered by the glomerulus & there’s no transporter to reabsorb it, what will happen to it by default?

it will be excreted into the urine - if something is filtered & not reabsorbed it WILL be excreted in the urine (even if it isn’t secreted into the tubule)

the kidneys dispose of compounds in the circulation by DEFAULT; there doesn’t HAVE to be a specific transport protein to get rid of a substance in the circulation

this is how the kidney can clear drugs/foreign compounds that shouldn’t be in the circulation

Osmole (Osm, osmol)

a unit of measurement that defines the number of moles of solute that contribute to the osmotic pressure of a solution

What is the important different between the kidney cortex & medulla?

the concentration of solutes in each’s interstitial space differs

the interstitial osmolality in the cortex is close/nearly identical to plasma’s, ~300 milliosmoles

the interstitial osmolality in the medulla is MUCH HIGHER, can reach up to ~1200 milliosmoles

this is key for generating concentrated (↑solute ↓water) urine, especially when trying to conserve water

Nephron

the basic functional unit of the kidney

it’s a blunt end tube w/ a glomerulus (where filtration occurs) → tubule that fluid makes its way through → empties into a collecting duct that continues into a series of larger and larger ducts that collect in the renal pelvis → ureter

e/a kidney has ~ 1.2 * 106 nephrons

if you have 2 kidneys there are ~2.4 million nephrons working to process all this fluid

What percentage of the Cardiac Output (C.O.) do the kidneys receive?

~25%

even though they only make up .5% of the body’s weight

they’re processing all this fluid - they don’t NEED 25% of the body’s O2 nor do they produce 25% of its CO2

can release renin in response to low BP, which is a protease that cleaves angiotensinogen into angiotensin I

the general function of the cells/renin is to “help control the constriction of these arterioles”

What renal disease occurs as a result of a defect in the nephrin protein?

Nephrotic Syndrome (loss of protein in urine)

is normally a transmembrane protein embedded in the podocyte membrane that makes up the filtration slits by interdigitating w/ each other (provide the way through which water/small molecules pass through the 3 layer capillary membrane)

if mutated, proteins from the plasma can get into the filtered fluid & get excreted in the urine (protein is NOT normally found in the urine)

it can cause edema & eventually renal failure

Glomerular Filtration Rate (GFR)

the rate at which fluid is filtered through the glomerulus (mL/min)

total volume of fluid being filtered by the kidneys from all the working nephrons

Renal Plasma Flow (RPF)

the rate at which plasma is delivered to the kidneys (mL/min)

both GFR & RPF are important indicators of renal function (aka how well the kidneys are working; abnormalities can be indicators of disease)

Glomerulonephritis

• renal disease often initiated by an immune response to a remote infection (eg. streptococcus bacteria) - 1 of the symptoms is a reduced GFR

Why has the oncotic pressure preventing filtration INCREASED (become more negative, 28 → 35) in the efferent arteriole end of the glomerulus?

b/c in the afferent end, filtration was promoted by hydrostatic pressure differences across the capillary membrane

filtration has decreased the amount of fluid dissolving solutes in the efferent plasma

the protein concentration has increased due to less fluid present (higher oncotic pressure results, preventing filtration from occurring)

How does tubular obstruction (eg. kidney stones) affect filtration?

it increases the PBS (bowman’s space hydrostatic pressure) so that will RETARD filtration

fluid from inside the capillary will have to work harder to get into the Bowman’s space, less will eventually make it out

Renal Blood Flow (RBF)

is typically around 1250 mL/min

this corresponds to ~25% of C.O.

Hematocrit (Hct)

the fraction of blood volume occupied by cells

is typically about 0.45

Renal Plasma Flow (RPF)

is the RBF * (1 minus the hematocrit)

RPF = RBF * (1 - Hct)

RPF = 1250 mL/min * 0.55 = 687 mL/min

Filtration Fraction (FF)

the fraction of plasma filtered through the glomerulus; usually ~0.2 (the fraction of plasma that enters the glomerulus that ACTUALLY gets filtered)

FF = GFR/RPF, or

GFR = FF * RPF

GFR=0.2*687 mL/min=137 mL/min

Typical Values

Renal Plasma Flow: 687 mL/min

Glomerular Filtration Rate: 137 mL/min

Renal Clearance (mL/min)

the volume of plasma per unit time from which substance x has been completely removed & excreted (in the urine)

Cx = UxV/Px

the renal clearance of a given substance is equal to its excretion rate divided by its concentration in the plasma

Values in Clearance Formula

Excretion Rate of x (mg/min): UxV

Ux: concentration of x in the urine (mg/mL)

V: urine flow rate (mL/min)

Px: concentration of x in the plasma (mg/mL)

Clearance v. Excretion

NOT the same thing

clearance is a volume/time - volume of plasma that’s been CLEARED of some compound

excretion is a mass/time - how much of the compound is being eliminated in the urine

The GFR can be measured using the CLEARANCE of a compound that has WHAT properties (4)?

1. it’s freely filtered: not bound to plasma proteins

2. not reabsorbed or secreted by the renal tubule: it has no transporter in either direction (the only way it gets into tubule is by filtration)

3. not metabolized or produced by the kidney

4. it DOESN’T alter the GFR

• the idea is to get a compound that’s filtered in exact proportion to the plasma; if 20% of the plasma gets filtered, 20% of compound x gets filtered

Inulin

a compounds that has the 4 aforementioned properties: a small polymer of fructose that isn’t metabolized

the amount of it that gets in the tubules gets excreted in the urine

GFR = Cinulin

= UinulinV/Pinulin

= (125 mg/mL*1 mL/min)/1 mg/mL

= 125 mL/min

(the urine flow rate is typically 1 mL/min & the concentration being infused into said patient is 1 mg/mL)

Why is the measured concentration of inulin in the urine (125 mg/mL) WAY higher than what it was in the plasma (1 mg/mL)?

b/c the majority of water diluting inulin in the plasma is reabsorbed during passage through the renal tubules, leaving less water in the urine & a more concentrated value there for inulin

Rate of Filtration of Inulin

that would be = to GFR * concentration of inulin in the plasma (GFR*Pinulin)

would give you the mass of inulin being filtered per minute

Excretion Rate of Inulin

the concentration of inulin in the urine * urine flow rate (Uinulin*V)

that’s the mass of inulin excreted per minute

Why do the Rate of Filtration & Excretion Rate of Inulin have to be equal?

b/c the only way inulin got INTO the urine is via filtration (there’s no secretion of it)

What is typically used to measure GFR instead of inulin (b/c it requires infusion)?

CREATININE: produced endogenously in skeletal muscle at fairly constant rate by creatine breakdown of

is freely filtered & not reabsorbed

GFR = Ccreatinine

= UcreatinineV/Pcreatinine

(a small amount is secreted by the renal tubule (10%), this error is offset by a 10% overestimate in the assay for plasma creatinine)

What kind of compound can be used to calculate Renal Plasma Flow (RPF)?

1. freely filtered at glomerulus

2. efficiently secreted from plasma into renal tubule

3. not reabsorbed from the renal tubule back into the blood

eg. PAH (para-aminohippuric acid), a small organic anion that must be infused

What is a complication of using PAH as an indicator of RPF?

not all of the PAH entering the afferent arteriole actually gets excreted in the urine

the transporter used to secrete it in the tubule isn’t efficient enough to clear it all; only ~90% of it is secreted into the tubule (extraction efficiency is 0.9) some ends up getting back into the circulation

• Reabsorption: increases linearly up until Pgluc = 3 mg/mL; at this point it levels off b/c the max reabsorption rate has been reached; transporters in the proximal tubule are saturated, so no more can be reabsorbed → glucose appears in urine